Time Resolved Breast Imaging Using a Combined MRI and Optical Tomography Approach

描述（由申请人提供）：原发性全身（新辅助）治疗通常用于局部晚期乳腺癌患者术前，以降低疾病阶段并增加成功结果的机会。然而，许多患者对新辅助治疗没有反应，最好换一种不同的治疗方案，或立即进行手术。然而，治疗监测是困难的，因为目前的临床检查和x线/超声乳房x线摄影随访与最终治疗病理结果相关性很差。磁共振成像（MRI）和正电子发射断层扫描（PET）已被评估为反应的早期预测指标，研究表明，18F-FDG PET以及扩散加权（DW） MRI和胆碱化合物磁共振波谱（tCho-MRS）测量结果与治疗开始后几周内的治疗成功相吻合。不幸的是，可用性（PET）、复杂性（tCho-MRS）和特异性（MRI）限制了这些方法的适用性。因此，有必要开发非侵入性的特定早期预测方法，使其更容易融入医疗实践。近红外光谱和断层扫描（NIRS-DOT）可能提供一个潜在的答案。NIRS-DOT是一种新型的功能成像技术，可以提供组织发色团的图像，如氧（HbO）和脱氧血红蛋白（HbR）、水和脂质，小型研究表明，它可能在治疗开始后一周就能高精度地预测治疗结果。此外，最近的技术进步已经允许DOT达到高时间分辨率（bbb1hz），允许通过动态成像探测新型功能信息。特别是，我们的小组已经获得了有希望的初步结果监测乳房组织对外部压迫的反应。组织对压迫的粘弹性反应导致血液动力学（血容量）变化，具有双相时间剖面，可能区分健康组织和乳腺病变。此外，血液动力学和组织氧代谢的相互作用导致血红蛋白氧合瞬变，提供了从时间分辨光学数据估计组织耗氧量（OC）和血流（BF）的机会。本提案的总体目标是将MRI和NIRS-DOT相结合，以表征组织血流动力学、血流和耗氧量的压缩测量作为对治疗进展敏感的新生物标志物的预测价值，并量化它们与最终病理结果的关系。来自MRI扫描的结构信息将用作光学重建的先验信息，动态光学和hbr相关MR血氧水平依赖（BOLD）图像将同时获得，从而实现融合方法，用于重建时间分辨的血流动力学图和BF/OC分布。不同的BOLD图像将与相应的HbR地图进行交叉验证。这项工作将以临床试验结束，以评估新的生物标志物的早期治疗结果预测能力。

DESCRIPTION (provided by applicant): Primary systemic (neoadjuvant) therapy is routinely used for locally advanced breast cancer patients before surgery to down-stage the disease and increase the chances of a successful outcome. Many patients though do not respond to neoadjuvant therapy, and may be better off switching to a different treatment regime, or progressing to surgery immediately. However, therapy monitoring is difficult because current clinical examination and x-ray/ultrasound mammography follow-ups correlate poorly with final therapy pathological outcome. Both magnetic resonance imaging (MRI) and positron emission tomography (PET) have been evaluated as early predictors of response, with studies showing that 18F-FDG PET as well as diffusion weighted (DW) MRI and choline-compounds MR spectroscopy (tCho-MRS) measurements correspond well with therapy success within a few weeks from the beginning of treatment. Unfortunately, availability (PET), complexity (tCho-MRS), and specificity (MRI) limit the applicability of these methods. Consequently, there is a need to develop non-invasive specific early prediction approaches that more easily integrate into medical practice. A potential answer may be offered by near infrared spectroscopy and tomography (NIRS-DOT). NIRS-DOT is a novel functional imaging technique that can offer images of tissue chromophores such as oxy (HbO) and deoxy hemoglobin (HbR), water and lipids, and small studies have hinted at its potential to predict therapy outcome with high accuracy as early as one week after the start of treatment. Further, recent technological advancements have permitted DOT to reach high time resolution (> 1Hz), allowing new types of functional information to be probed by dynamic imaging. In particular, our group has obtained promising initial results monitoring the response of breast tissue to external compression. Tissue viscoelastic response to compression causes hemodynamic (blood volume) changes with bi-phasic temporal profiles likely to differentiate healthy tissues from breast lesions. Further, the interplay of hemodynamics and tissue oxygen metabolism leads to hemoglobin oxygenation transients that offer the opportunity to estimate tissue oxygen consumption (OC) and blood flow (BF) from time-resolved optical data. The overall goal of this proposal is to combine MRI and NIRS-DOT to characterize the predictive value of compression-enabled measurements of tissue hemodynamics, blood flow and oxygen consumption as new biomarkers sensitive to therapy progress and quantify their relationship to final pathological outcome. Structural information from the MRI scans will be used as prior information for the optical reconstructions and dynamic optical and HbR-related MR blood oxygen level dependent (BOLD) images will be simultaneously acquired enabling a fusion approach for reconstructing time-resolved hemodynamic maps and BF/OC distributions. Difference BOLD images will be cross-validated against corresponding HbR maps. The work will culminate with a clinical trial to assess the early therapy outcome predictive ability of the new biomarkers. PUBLIC HEALTH RELEVANCE: We propose to use fast optical tomography during breast compression to investigate biomechanical and metabolic characteristics of normal and lesion tissues, with the goal of improving specificity for cancer diagnosis and non-invasively monitoring chemotherapy progress.